The skin is an organ located on the outermost layer of the body, and is continuously exposed to stimulation from the outside such as ultraviolet rays, physical stimulation, chemical stimulation or biological invasion.
The skin has a three-layer structure consisting of the epidermis, dermis and subcutaneous tissue, and among these, the epidermis of the outermost layer is composed of keratinocytes, Langerhans cells and melanocytes and the like, and functions to prevent water loss and entry of foreign bodies and to protect the body from ultraviolet rays and other elements of the external environment. Upon receiving external stimulation, keratinocytes release a stimulation response factor, and then surrounding keratinocytes which receive the signal of the released stimulation reaction factor secrete inflammatory cytokines, which result in induction of immune cells, and the occurrence of inflammation at the stimulated site (Non-Patent Document 1). In addition, it has been determined from recent research that Langerhans cells fulfill an important role in the immune function of skin through antigen processing and their antigen presenting ability. Langerhans cells promptly make contact with and process antigens entering from the outside as foreign bodies, transport them to lymph nodes and present them to T cells followed by induction of a series of immune response reactions. As a result, Langerhans cells have been determined to contribute to functions that counter chemical stimulation and biological invasion. On the other hand, Langerhans cells express CD39, which functions as an ATPase, and as a result thereof, has the ability to lower the amount of ATP, an extracellular stimulation response factor (Non-Patent Document 2). Extracellular ATP is recognized to be one of the signals of the inflammatory process. Thus, Langerhans cells are thought to reduce skin disorders caused by ultraviolet rays or physical stimulation by contributing to the reduction of inflammation by mediating the degradation of extracellular ATP. It has been reported that, when the number of Langerhans cells decreases due to zinc deficiency, the function of CD39 molecules of sedating the response of skin to external stimulation decreases, thereby resulting in an excessive response to stimulation that causes excessive inflammation (Non-Patent Document 3).
Thus, since enhancement of skin immune function, decreased inflammation and reduction of sunburn and other skin disorders can be expected to be realized by increasing or activating Langerhans cells, screening methods using Langerhans cells as an indicator (Patent Document 1) and pharmaceutical reagents or reduction inhibitors that increase or activate Langerhans cells (Patent Document 2) are being developed.